| Project/Area Number |
20K16216
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 多発性骨髄腫 / マウスモデル / マイクロRNA / 核酸医薬 / miR-143 |
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| Outline of Research at the Start |
既存治療薬に不応である多発性骨髄腫は全身障害を伴う重篤な症状を来しうるにもかかわらず有効な治療手段が少ない.この薬剤不応性にRAS変異の関与が示唆されているが，RASタンパクは低分子化合物の開発が難しく，多数の代償活性化機構を持つため単独阻害では治療効果が限定的である.そこで本研究では，我々が開発した1)RNA干渉によりRASのみならずエフェクター経路の複数分子(Akt，ERK，SOS1)を同時に抑制でき，2)化学的修飾およびLNP包埋によりRNase 耐性と腫瘍送達性が向上したmiR-143#12-LNPを用いてKRAS 変異ヒト骨髄腫の治療法開発を試みる．
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| Outline of Final Research Achievements |
Effective treatments for KRAS-mutant multiple myeloma are limited. The present study evaluated the antitumor potential of chemically modified microRNA-143 (CM-miR-143), which regulates the entire RAS molecular network by RNA interference, in a KRAS-mutant multiple myeloma mouse model. The result showed that administration of CM-miR-143 significantly reduced the amount of tumor cells distributed in the spleen, as well as the expression of the miR-143 target gene ERK1/2 and the proliferation marker p-Histone H3. On the other hand, no significant antitumor effect was observed in tumor cells distributed to the bone marrow. These findings demonstrated that CM-miR-143 induced significant antitumor effects in a multiple myeloma model, although it has organ specificity.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、KRAS変異多発性骨髄腫に対しては有効な治療法が限られている。今回の研究によって、KRAS変異多発性骨髄腫に対する、miR-143を使用した核酸医薬の有効性と特徴を明らかにした。
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